The present invention is directed to chiral, N-substituted .alpha.-amino acids. The present invention is also directed to an improved synthetic route to chiral N-substituted .alpha.-amino acids. The synthesis requires two steps, the first involving a condensation of a chiral, N-protected, .alpha.-amino acid with an aldehyde to form an oxazolidinone. The second step, reductive cleavage of the oxazolidinone C-O bond gives, without affecting either the N-protecting group, or the desired chirality, the N-protected, N-substituted .alpha.-amino acid.
A standard method of preparing N-protected, N-methyl amino acids is described in McDermott and Benoiton, Canadian Journal of Chemistry, 51, 1915 (1973) and Cheung and Benoiton, Canadian Journal of Chemistry, 55, 906 (1977). The procedure involves alkylation of an N-protected amino acid in the presence of sodium hydride. The process fails for certain amino acids and is limited to the formation of N-methyl amino acids.
Unprotected N-methyl amino acids have been prepared by the catalytic hydrogenation of an oxazolidinone intermediate formed by the reaction of an N-protected .alpha.-amino acid and paraformaldehyde. See for example, Pless in Swiss Patent No. 597,151 (Derwent No. 27069A). This method is limited to the production of N-methyl .alpha.-amino acids.
The synthetic method of the instant invention has several advantages over the prior art; (1) the reaction is more general, in that it is not limited to the formation of N-methyl amino acids, (2) the present invention utilizes acid-catalyzed conditions, and (3) the chirality of the starting material is preserved. Acidic conditions allow for the use of base sensitive protecting groups, thus giving versatility to the reaction sequence See for example, Meienhofer, U.S. Pat. No. 4,108,846. By the terms "preserving chirality", it is understood that the process of the present invention does not effect any change in the chiral center of the starting .alpha.-amino acid. That is, for example, L-amino acids will retain the "L" configuration when N-substituted under the present process.